BACKGROUND:Previous studies have confirmed that Wen-Shen-Tong-Du Decoction can promote the recovery of spinal cord injury by inhibiting pyroptosis of splenic B cells,promoting the phagocytosis of myelin debris by microvascular endothelial cells,affecting the migration and infiltration of microglia,promoting the recovery of damaged neurons,and decreasing neuronal apoptosis after spinal cord injury,but the mechanism of this is still not clear. OBJECTIVE:To investigate the effect of Wen-Shen-Tong-Du Decoction on the triggering receptor expressed on myeloid cells 2(TREM2)and PI3K/Akt signaling pathways in mice following spinal cord injury. METHODS:Thirty-six C57BL/6 mice were selected and randomly divided into a sham-operation group,a model group and a Wen-Shen-Tong-Du Decoction group,with 12 mice in each group.In the model and Wen-Shen-Tong-Du Decoction groups,mouse models of T10 spinal cord injury were prepared by the modified Allen's method.On the 1st day after modeling,the Wen-Shen-Tong-Du Decoction group was given Wen-Shen-Tong-Du Decoction by gavage,and the sham-operation group and the model group were given saline by gavage once a day for 28 days.During the drug administration period,mouse motor function was evaluated by Basso Mouse Scale score and inclined plane test.On the 7th and 28th days after modeling,hematoxylin-eosin staining was used to observe the histopathological changes in the spinal cord tissue of the mice;immunofluorescence double staining was used to detect the protein expression of ionized calcium binding adaptor molecule 1(IBA1)and TREM2;and western blot assay was used to detect the expression of TREM2,PI3K,p-PI3K,Akt,p-Akt,Bcl2,Bax and Caspase3 in spinal cord tissue. RESULTS AND CONCLUSION:Basso Mouse Scale scores and inclined plane test results indicated that the motor function of the mouse hindlimbs was declined after spinal cord injury,and Wen-Shen-Tong-Du Decoction significantly improved motor function in mice with spinal cord injury.Hematoxylin-eosin staining results revealed that Wen-Shen-Tong-Du Decoction significantly ameliorated the pathological structure of spinal cord tissue compared with the model group,manifesting as reduced degrees of dorsal white matter and neuronal atrophy,decreased cytoplasmic vacuolization,and reduced inflammatory cell infiltration.Immunofluorescence double staining results showed that on the 7th day after modeling,the protein expression of IBA1 and TREM2 in the model group was lower than that in the sham-operation group(P＜0.05),and the protein expression of IBA1 and TREM2 in the Wen-Shen-Tong-Du Decoction group was higher than that in the model group(P＜0.05);on the 28th day after modeling,the protein expression of TREM2 in the model group was lower than that in the sham-operation group(P＜0.05),and the protein expression of TREM2 in the spinal cord tissue of the mice in the Wen-Shen-Tong-Du Decoction group was higher than that in the model group(P＜0.05).Western blot results analysis demonstrated that on the 7th day after modeling,compared with the sham-operation group,the model group exhibited a significant reduction in TREM2,PI3K,and Bcl2/Bax(P＜0.05),as well as a significant increase in p-Akt,Bax and p-Akt/Aktp-PI3K(P＜0.05);compared with the model group,the Wen-Shen-Tong-Du Decoction group showed a significant increase in TREM2,PI3K,p-PI3K,Akt,p-Akt,Bcl2,p-PI3K/PI3K,p-Akt/Ak,and Bcl2/Bax(P＜0.05),as well as a significant decrease in Bax and Caspase3 protein expression(P＜0.05).On the 28th day after modeling,compared with the sham-operation group,the model group exhibited a significant reduction in TREM2,PI3K,p-PI3K,Akt,p-Akt,Bcl2 and Bcl2/Bax(P＜0.05),as well as a significant increase in Bax protein expression(P＜0.05);compared with the model group,the Wen-Shen-Tong-Du Decoction group showed a significant increase in TREM2,PI3K,Akt,p-Akt,Bcl2,and Bcl2/Bax(P＜0.05),as well as a significant decrease in Bax protein expression(P＜0.05).To conclude,Wen-Shen-Tong-Du Decoction may activate the PI3K/Akt signaling pathway by up-regulating the expression of TREM2 protein in microglia,and then inhibit neuronal apoptosis,thus exerting neuroprotective effects and promoting the repair of spinal cord injury.

Linxian County in Henan Province, Northern China is known as the region with the highest incidence and mortality rate of esophageal cancer worldwide. Since 1959, the Henan medical team has conducted field work on esophageal cancer prevention and treatment in Linxian. Through three generations of effort exerted by oncologists over 65 years of research on esophageal cancer prevention and treatment in Linxian, the incidence rate of esophageal squamous cell carcinoma in this area has dropped by nearly 50%, and the 5-year survival rate has increased to 40%, reaching the international leading level. This article aims to summarize the history, present opportunities and new challenges, and explore the experience of esophageal cancer prevention and treatment in Linxian (referred to as the “Linxian experience”), providing reference and guidance to cancer prevention and treatment research in China.

Objective To investigatethe relationship between gastroesophageal reflux disease (GERD) symptoms and clinicopathological characteristics, p53 expression, and survival of Chinese patients with esophageal adenocarcinoma. Methods A total of 3882 patients with esophageal adenocarcinoma, 970 matched patients with esophageal squamous cell carcinoma, and 970 matched patients with gastric cardia adenocarcinoma were included to compare the incidence of GERD symptoms. Patients with esophageal adenocarcinoma were divided into two groups according to the presence and absence of GERD symptoms. The differences in clinicopathological characteristics and p53 expression between the two groups were compared by chi-square test, and the differences in survival between the two groups were compared by landmark analysis. Results The incidence of GERD symptoms increased successively in esophageal squamous cell carcinoma, esophageal adenocarcinoma, and gastric cardia adenocarcinoma. In patients with esophageal adenocarcinoma, the proportions of male, less than 65 years old, lower thoracic tumors, tumors without squamous cell carcinoma, poorly differentiation, early tumors (stage 0-I), and p53-positive tumors in the group with GERD symptoms were higher than those in the group without GERD symptoms; moreover, the long-term survival (≥15 years) was better. Conclusion GERD symptom is an important clinical sign of esophageal adenocarcinoma. It is closely related to specific clinicopathological characteristics, p53 overexpression, and good long-term prognosis.

Objective:To explore the association between cognitive function and the level of gamma-amino-butyric acid(GABA)in anterior cingulate cortex(ACC)before and after treatment in patients with major depres-sion disorder.Methods:Totally 31 medication-naive patients with major depression disorder meeting the criteria of the Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition(DSM-5)and 33 normal controls were col-lected.Each eligible patient received treatment with selective serotonin reuptake inhibitor agents for 8 weeks.The MATRICS Consensus Cognitive Battery(MCCB)was used to evaluate the cognitive function.By means of 1H magnetic resonance spectroscopy,anterior cingulate cortex GABA concentrations were measured.Results:At base-line,the concentration of ACC GABA relative to water(GABA+/W)was lower in the patient group than in the control group(P＜0.05)and increased after treatment(P＜0.05).ACC GABA+/W was negatively associated with verbal learning and visual memory score in patient group at baseline(correlation coefficient and P value were r=-0.40,P＜0.05;r=-0.42,P＜0.05,respectively).The ACC GABA+/W difference resulted of treatment in patient group was positively associated with the difference of working memory score and the difference of reasoning and problem-solving score(correlation coefficient and P value were r=0.58,P＜0.05;r=0.66,P＜0.05,respec-tively).Conclusion:The cognitive dysfunction of patients with major depression disorder may not be related to the degree of depression and anxiety.And improvement of cognitive function may be associated with increase of ACC GABA concentrations.

Anticoagulation therapy stands as a key treatment for thrombotic diseases. The consequential bleeding risk tied to existing anticoagulation methods significantly impacts patient prognosis. In the intensive care unit (ICU), patients often necessitate organ support, leading to the inevitable placement of artificial devices in blood vessels, thereby requiring anticoagulation treatment to avert clot formation that might impede organ support. Nevertheless, these patients commonly encounter a heightened risk of bleeding. Hemophilia B, identified in 1953, manifests as a deficiency in coagulation factor Ⅺ (FⅪ), which focused people's perspective on the endogenous coagulation pathway, that is, the contact pathway. Upon interaction between the surface of artificial devices and FⅫ, FⅫ activates, subsequently triggering FⅪ and initiating the "coagulation cascade" within the contact pathway. Inhibitors targeting the contact pathway encompass two primary categories: FⅫ inhibitors and FⅪ inhibitors, capable of impeding this process. This article reviews the role of FⅫ and FⅪ in activating the contact pathway, seeking to illuminate their contributions to thrombus formation. By listing the relatively mature drugs and their indications, clinicians are familiar with this new anticoagulant.

Objective:To study the effects of arsenic exposure on necroptosis pathway and inflammatory response of mouse myocardial cells.Methods:Sixty male C57BL/6J mice were randomly divided into control group (group C) and low, medium, and high dose arsenic exposure groups (groups L, M, H) based on body weight using a random number table method. Each group had 15 mice, and they drank 0.00, 0.15, 1.50, and 15.00 mg/L arsenic trioxide (As 2O 3) solution prepared with deionized water. The exposure period was 12 weeks. Hematoxylin-eosin (HE) staining and Masson trichrome staining of paraffin-embedded heart tissues were used to observe the histopathology changes of the heart. Transmission electron microscopy (TEM) was used to evaluate the ultrastructural changes of myocardial cells. The quantitative real-time PCR (qRT-PCR) was used to detect the mRNA expression of inflammatory genes [tumor necrosis factor (TNF)-α and interleukin(IL)-6] and the genes involved in necroptosis pathway [receptor-interacting protein (RIP) 1, RIP3 and mixed-lineage kinase domain-like protein (MLKL)]. Protein expressions of RIP1 and RIP3 in the heart were assessed by western blotting. Results:Histopathological examination results showed there were myocardial necrosis, inflammatory cells infiltration and fibroblasts hyperplasia and other changes in groups M and H. TEM analysis revealed marked ultrastructural changes in groups M and H, including fractured myofibril, fractured Z lines of sarcomere, and swollen mitochondria with fractured cristae. Compared with group C (1.00 ± 0.00), the mRNA expression of RIP1 in group H was significantly up-regulated (1.41 ± 0.06, P < 0.05); the mRNA expressions of RIP3 (1.29 ± 0.14, 1.56 ± 0.08), MLKL (1.23 ± 0.05, 1.36 ± 0.07), TNF-α (2.20 ± 0.10, 2.23 ± 0.18) and IL-6 (1.87 ± 0.16, 1.63 ± 0.15) were significantly up-regulated in groups M and H ( P < 0.05). The protein expressions of RIP1 (0.43 ± 0.04, 0.50 ± 0.04) and RIP3 (0.68 ± 0.02, 0.84 ± 0.05) in groups M and H were higher than those in group C (0.25 ± 0.01, 0.45 ± 0.04, P < 0.05). Conclusion:Subchronic arsenic exposure induces histopathological changes such as myocardial necrosis and fibrosis in mice, inducing necroptosis and inflammatory reactions in myocardial cells.

ObjectiveTo explore the effects and possible mechanism of Wenshen Tongdu Formula （温肾通督方， WTF） on spinal cord injury. MethodsThirty-six C57BL/6 female mice were randomly divided into sham operation group， model group and WTF group， with 12 mice in each group. The spinal cord injury model was established in the model group and the WTF group using the modified Allen's method， while in the sham operation group the spinal cord was only exposed. Since the 1st day after surgery， 50 g/（kg·d） of WTF solution was given to the WTF group by gavage， while 20 ml/（kg·d） of normal saline was given to the sham operation and model group by gavage， all for 14 days. Before surgery and on the 1st， 7th， and 14th days after surgery， the motor function of the mice was evaluated using the inclined plane test and hind limb motor function score （by BMS）. On the 3rd day after surgery， the nerve electrophy-siology was detected through electromyography and motor evoked potential； the spleen length was measured， and B cells in the spleen were sorted by magnetic beads； the differential expression of proteins were detected through proteomics technology； and the protein expression of mitochondrial outer membrane transport porin 20 （Tom20） and downstream cleaved caspase-3 in spleen B cells were measured using Western blotting. On the 14th day after surgery， MRI was used to observe the recovery of the spinal cord. ResultsCompared to those in the sham operation group at the same time， the BMS scores and subscores and the inclined plane test angle in the model group were reduced on the 1st， 7th and 14th days after surgery； the peak value of electromyogram and motor evoked potential were reduced， and the spleen length was shortened， while the expression of Tom20 and cleaved caspase-3 increased in splenic B cells increased （P＜0.05）. Compared to those in the model group at the same time， the BMS subscores on the 14th day and the angle of the inclined plane test on the 7th and 14th days after surgery increased in the WTF group； the peak value of electromyography and motor evoked potential， as well as the length of spleen increased， and the expression of Tom20 and cleaved caspase-3 decreased （P＜0.05）. The proteomics results showed that there were 100 differential proteins in the WTF group versus the model group， of which 37 were up-regulated and 63 were down-regulated. GO enrichment analysis showed that differential proteins mainly played their roles in oxygen binding， exogenous apoptosis negative feedback， zinc ion response， and oxygen transport. KEGG enrichment analysis showed that differential proteins were mainly concentrated in metabolic pathways， Huntington's disease， oxidative phosphorylation and other pathways. Subcellular localization showed that differential proteins were associated with mitochondria. Magnetic resonance imaging on the 14th day after surgery showed that the spinal cord structure of the mice in the sham operation group was intact， and the segments were clear， with normal spinal cord signal； the low signal area in the spinal cord injury area increased in the model group， and the spinal cord became significantly thinner； the injured segment had obvious depression in the WTF group， but the structure was more complete than that in the model group. ConclusionWTF may promote spinal cord injury repair by regulating immune function， and its mechanism may be related to inhibiting pyroptosis of spleen B cells.

Objective:To analyze the risk factors of bronchopulmonary dysplasia(BPD)in very preterm infants(VPI), and to provide scientific basis for the prevention and treatment of BPD in VPI.Methods:A prospective multicenter study was designed to collect the clinical data of VPI in department of neonatology of 28 hospitals in 7 regions from September 2019 to December 2020.According to the continuous oxygen dependence at 28 days after birth, VPI were divided into non BPD group and BPD group, and the risk factors of BPD in VPI were analyzed.Results:A total of 2 514 cases of VPI including 1 364 cases without BPD and 1 150 cases with BPD were enrolled.The incidence of BPD was 45.7%.The smaller the gestational age and weight, the higher the incidence of BPD( P<0.001). Compared with non BPD group, the average birth age, weight and cesarean section rate in BPD group were lower, and the incidence of male infants, small for gestational age and 5-minute apgar score≤7 were higher( P<0.01). In BPD group, the incidences of neonatal respiratory distress syndrome(NRDS), hemodynamically significant patent ductus arteriosus, retinopathy of prematurity, feeding intolerance, extrauterine growth restriction, grade Ⅲ~Ⅳ intracranial hemorrhage, anemia, early-onset and late-onset sepsis, nosocomial infection, parenteral nutrition-associated cholestasis were higher( P<0.05), the use of pulmonary surfactant(PS), postnatal hormone exposure, anemia and blood transfusion were also higher, and the time of invasive and non-invasive mechanical ventilation, oxygen use and total hospital stay were longer( P<0.001). The time of starting enteral nutrition, cumulative fasting days, days of reaching total enteral nutrition, days of continuous parenteral nutrition, days of reaching 110 kcal/(kg·d) total calorie, days of reaching 110 kcal/(kg·d) oral calorie were longer and the breastfeeding rate was lower in BPD group than those in non BPD group( P<0.001). The cumulative doses of amino acid and fat emulsion during the first week of hospitalization were higher in BPD group( P<0.001). Multivariate Logistic regression analysis showed that NRDS, invasive mechanical ventilation, age of reaching total enteral nutrition, anemia and blood transfusion were the independent risk factors for BPD in VPI, and older gestational age was the protective factor for BPD. Conclusion:Strengthening perinatal management, avoiding premature delivery and severe NRDS, shortening the time of invasive mechanical ventilation, paying attention to enteral nutrition management, reaching whole intestinal feeding as soon as possible, and strictly mastering the indications of blood transfusion are very important to reduce the incidence of BPD in VPI.

【Objective】 In recent years, granulocyte colony stimulating growth factor (G-CSF) has been proved to be expressed in the posterior capsule of the lens of posterior capsular opacification (PCO), but its specific role remains unclear. The purpose of this study was to explore whether G-CSF plays a role in PCO. 【Methods】 First, human lens epithelial cells (HLEC-B3) were treated with different concentration of recombinant G-CSF protein and screened for effective appropriate concentration. Then, Western blotting was used to detect the effects of extracellular matrix (ECM) synthesis and epithelial mesenchymal transdifferentiation (EMT) marker genes after G-CSF treatment on HLEC-B3 cells. Finally, the effects of G-CSF treatment on the migration and invasion of HLEC-B3 cells were detected by scratch experiment and Transwell test. 【Results】 G-CSF at 80 μg/L could promote the proliferation of HLEC-B3 cells. After G-CSF was treated for 48 h, the expressions of EMT and ECM synthesis marker genes in HLEC-B3 cells were significantly upregulated with time. G-CSF could significantly promote HLEC-B3 cell invasion after 48 h induction. Similarly, G-CSF could also significantly induce cell migration compared to the CTRL group. 【Conclusion】 G-CSF can promote the proliferation, migration and invasion of HLEC-B3 cells, as well as EMT and ECM synthesis, which might be involved in the occurrence of PCO. Inhibiting the expression of G-CSF may be a new strategy for PCO prevention.

Objective:To retrospectively analyze the clinical and serological characteristics in rehabilitated patients with common novel coronavirus pneumonia(COVID-19).Methods:A total of 165 patients with common COVID-19 were enrolled in this retrospective study, in which clinical data was collected from February 23 to March 15, 2020 in Leishenshan Hospital(Wuhan, China). The patients with COVID-19 were divided into elderly group and non-elderly group according to their age, and the differences in the clinical and serological metabolic characteristics between these two groups were analyzed.Results:49.7% patients were over 60 years old. The most common clinical symptoms were fever, cough, and fatigue, followed by muscle soreness. Expectoration and digestive tract symptoms were rare. Dyspnea occurred more frequently in the elderly group than in non-elderly group(47.56% vs 25.30%, P<0.01). Hypertension was the most common concomitant disease(accounting for 29.1%)followed by diabetes. Hypertension was more common in the elderly group than in non-elderly group(41.46% vs 16.86%, P<0.01), but without significant difference in diabetes between the two groups. The counts of leukocytes and lymphocytes in all patients were in the normal range, and no difference was observed between the groups. The comparison of serological indicators showed that serum creatinine in the elderly group was higher than that in the non-elderly group( P<0.01)while serum albumin, glomerular filtration rate, and serum calcium were lower in the elderly group. After serum albumin correction, the levels of albumin corrected calcium in all patients were in the normal range, without significant difference between these two groups. There was no significant difference between the two groups when the length of hospital stay was taken as the index of outcome [(34.01±10.24) vs(30.97±10.51)d, P>0.05]. Conclusion:Fever, cough, and fatigue are the most common clinical symptoms in patients with ordinary COVID-19. The elderly are more likely to develop dyspnea. The blood routine and metabolic characteristics in patients with common COVID-19 are normal, but serum albumin level is more likely to decrease in elderly patients with COVID-19.